The goal of this application is to characterize the kinases that are activated by chemotactic factors, specifically those kinases which are not activated by protein kinase C dependent mechanisms , and to identify the substrates of these kinases. The ultimate goal is to understand the role of these kinase pathways in neutrophil activation and function in response to chemotactic factors, cytokines or crosslinking of Ff receptors. The specific aims are, first, to continue to define the protein Kinases that are activated in response to the above mentioned stimuli and specifically those which are not protein kinase dependent. The specific projects will concentrate upon activation and regulation of three kinases in this Specific Aim. 1) MAPKAP-kinase 2, 2) (PKH4) protein kinase histone 4 and 3) calcium-calmodulin-dependent protein kinase II (CAMPKII). Specific aim 2 will concentrate on further definition on the phosphoproteins of these kinases. Much of this work concentrate on the recently identified substrate of the MAPKAP-kinase, (LSP1) lymphocytes specific protein 1. In addition, various assays of neutrophil function will be performed, using relatively specific inhibitors of different kinases and intrinsic kinase activity of these kinases in control cells in stimulated cells will be performed using immunoprecipitation and in vitro kinase assays.